Lung cancer risk remains high; smoking more important than any HIV factor in heart attack risk

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Smoking probably contributes far more to the risk of
cardiovascular disease in people with HIV than antiretroviral drug choice, viral load or any factor linked to
the virus, but stopping smoking leads to a rapid reduction in the risk of some
cancers, according to results from a cluster of studies presented at the 2017
Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle on Thursday.

Smoking is far more common among people living with HIV than
in the general population. In the United States general population, the
prevalence of smoking has declined from 42% in 1965 to 17% in 2014, but a 2015
study estimated that 40% of people living with HIV in the United States still
smoke. In the United Kingdom the
ASTRA cohort study found that people with HIV were more likely to smoke
than the general population (29% vs 19%), and in particular, were far more
likely to be heavy smokers.

A recently published study estimated that smoking has a greater impact on the life expectancy of people with HIV than HIV infection that is well controlled by treatment, due to cancers, cardiovascular disease and chronic obstructive pulmonary
disease.

Smoking cessation and cancer risk

Smoking is a major risk factor for numerous cancers,
especially lung cancer. What is less clear is whether, in people living with
HIV, the risk of various cancers begins to fall after people stop smoking.
Although the risk of lung cancer begins to fall in the general population after
people stop smoking, it is not known if the same is true in people with HIV.

To answer this question Leah Shepherd of University College
London and researchers on the D:A:D cohort study looked at the risk of
developing various cancers among former smokers in the cohort. The study looked
at cancer incidence in all study participants between 2004 and 2015, and
compared outcomes between people who were smokers, never-smokers, people who
were ex-smokers at the time they entered the study, and people who gave up
smoking during the study period.

Ex-smokers were stratified according to whether they had
given up less than a year ago, 1-2 years ago, 2-3 years ago, 3-5 years ago, or
at least five years ago. Study participants were followed for a median of nine
years.

A total of 1980 cancers were diagnosed among 35,424 participants (242
lung cancers, 487 other cancers recognised as smoking-related, and 1251 not
related to smoking), 46% of whom were smokers and 20% ex-smokers.

Lung cancer occurred overwhelmingly in current (70%) or
ex-smokers (21%). Other smoking-related cancers such as head and neck,
oesophageal, stomach, pancreatic, kidney and urinary, ovarian and liver cancer,
also occurred predominantly in smokers (52%) and ex-smokers (21%). Cancers not
related to smoking were also more commonly diagnosed in smokers (47%) and
ex-smokers (20%).

Crude analysis of incidence showed that the risk of
smoking-related cancers (excluding lung cancer) fell very substantially more
than a year after quitting and thereafter it was comparable to the risk of
people who had never smoked. Age, gender and
CD4 cell count did not affect cancer risk in any analysis.

On the other hand, lung cancer incidence remained at least
eight times higher in ex-smokers five years after giving up when compared to
people who had never smoked (aRR:
8.26 95%CI: 2.83, 24.09). This finding is in contrast to observations in
HIV-negative people, where a decline in the risk of lung cancer begins to become
detectable within five years of stopping smoking.

The study is
limited in its power to explore some of the factors known to influence
smoking-related cancer risk, such as smoking intensity and the duration of
smoking, because of a lack of data. Leah Shepherd said that longer-term
follow-up of cancer risk in people with HIV will be needed to provide more
information about risk, especially for lung cancer.

Risk factors for heart attack

Smoking emerged
as one of the most important risk factors for heart attack in an analysis of 29,515
people with HIV receiving care in North America, presented by Keri Althoff of
Johns Hopkins University, Baltimore. The study set out to determine what
proportion of heart attacks in the population of people with HIV were
attributable to various risk factors.

These included, on the one hand, the
well-established risk factors: smoking, high cholesterol, treated hypertension,
diabetes, body mass index (BMI) of 30 or above and stage 4 chronic kidney disease.
The analysis also looked at the contribution of HIV-specific risk factors: CD4
count below 200, lack of viral suppression, an AIDS diagnosis, and HCV
infection.

The NA-ACCORD
cohort study recorded 347 heart attacks among participants during a median
follow-up period of 3.5 years.

The prevalence of
smoking in the cohort was extremely high: 75% in people who did not experience
a heart attack, and 84% in those who did. Smokers were 80% more likely to have
a heart attack than never-smokers – similar to the risk of heart attack seen in
people with stage 4 kidney disease, diabetes or a current CD4 count below 200.
But this degree of risk was dwarfed by the risks attached to hypertension.
People with high blood pressure, even though it was being treated, were four
times more likely to have a heart attack than people without, and people with a
BMI of 30 or above and elevated cholesterol were three times more likely to
have a heart attack than those without elevated cholesterol. Surprisingly, high
cholesterol in the absence of obesity was not associated with an increased risk
of heart attack.

Considering the
contribution of these risk factors to the total number of heart attacks, three
stood out. If everyone stopped smoking 38% of all heart attacks would be
avoided. If everyone had normal cholesterol, 43% of heart attacks would be
avoided, and if everyone had normal blood pressure, 41% of heart attacks would
be avoided. In comparison, changing risk factors associated with HIV would have
a much smaller effect on the total number of heart attacks.

Keri Althoff drew
the attention of delegates to previous research from the same cohort study,
which found that stopping smoking would make the single greatest contribution
to cutting cancer diagnoses in people with HIV. Controlling cholesterol would
have greatest impact on end-stage kidney disease and on heart attack.

Similarly, modelling
of the burden of cardiovascular disease among people with HIV in the
Netherlands between 2015 and 2030 found that smoking cessation and cholesterol and
hypertension management would result in far greater reductions in
cardiovascular events than HIV-related interventions such as earlier diagnosis
and treatment or avoiding antiretrovirals with known cardiovascular risks.

The model,
presented by Rosan van Zoest of Amsterdam Institute for Global Health and
Development, used data from the Netherlands ATHENA cohort and the D:A:D study
to simulate cardiovascular disease over time. The model predicts that the
annual incidence of cardiovascular events will increase by 55% between 2015 and
2030, and that improving the rate of smoking cessation would reduce the number
of heart attacks by 6-13% each year. However, the model makes the ambitious
assumption that it will be possible to achieve cessation rates of 50% or 100%.
In clinical settings, smoking cessation rates are much lower.

Taken together,
the findings suggest the need for a much greater emphasis on smoking cessation
in people with HIV, as well as a greater emphasis on management of cholesterol
and hypertension. All these interventions will require greater input from
primary care physicians in settings where these interventions are chiefly delivered
by general practitioners, and greater focus on non-HIV health care in settings
where HIV care is delivered by specialist providers.

NAM's coverage of CROI 2017 has been made possible thanks to support from Janssen and ViiV Healthcare.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends
checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member
of your healthcare team for advice tailored to your situation.